Challenging The Dogma Of Nodepositive And Nodenegative Breast Cancer

Consider two patients. The first has four negative sentinel lymph nodes and the second has a 5.5 mm metastasis in one of several lymph nodes. Five years after diagnosis, the first patient develops a cerebral metastasis and the second patient has a mammographic density adjacent to the old partial mastectomy site that is fibrocystic change on biopsy. A curious pathologist performs deeper sections and cytokeratin immunohistochemistry (CK IHC) on the "negative" sentinel nodes prior to tumor board because these were not performed at the time of diagnosis. One of the sentinel nodes contains a 0.1 mm metastasis and another node contains five clusters of tumor cells ranging from one to six cells in the subcapsular sinus. Now imagine the discussion at tumor board. Someone is sure to suggest "if we had only done the deeper sections and immunos five years ago ... ." This, of course, is the sort of magical thinking that propagates oncological myths. What are we missing in these two scenarios? Would the question still be asked if we had the whole story? The first patient was 47-years-old at the time of diagnosis and had a 2.2 cm moderately differentiated tumor she discovered on self-breast examination seven months after a negative screening mammogram. The tumor was estrogen and progesterone receptor negative and had no evidence for HER2/neu over-expression or amplification. She was treated with dose dense chemotherapy. The second patient was 68-years-old at the time of diagnosis. The tumor measured 1.3 cm in greatest dimension and was detected on screening mammogram. Comparison films from two previous examinations had revealed architectural distortion in the same area that was not appreciably different in size but was less dense than on the diagnostic index examination. In retrospect, it was undoubtedly a missed cancer that had been present for at least two years, probably longer. The tumor was well differentiated with strong and diffusely positive estrogen and progesterone receptors. She had been treated with tamoxifen, but did not receive chemotherapy. An astute medical student would now suggest that the younger woman had a biologically aggressive tumor and the postmenopausal woman had a biologically indolent tumor. In these two patients, the presence or absence of lymph node metastases had little influence on either treatment or outcome at five years.

These two cases are not meant to argue against the value of lymph node evaluation. Rather, they are meant to challenge the notion that lymph node status can be evaluated in a vacuum and to illustrate a fundamental principle: the intrinsic biology of a tumor is well established by the time a clinical or pathological diagnosis is established; intervention may or may not alter the ultimate outcome for any individual.

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